John Evans, Beam Therapeutics CEO

Beam re­veals what tripped up its base-edit­ed, off-the-shelf CAR-T as it tries to clear FDA hold

Last month, Beam Ther­a­peu­tics re­vealed the FDA in­tend­ed to place its pre­clin­i­cal off-the-shelf CAR-T ther­a­py on hold. To­day, the com­pa­ny re­vealed the rea­sons why.

Reg­u­la­tors are re­quest­ing four things be­fore they will con­sid­er lift­ing the hold, Beam wrote in an SEC fil­ing, in­clud­ing new da­ta and analy­ses re­gard­ing their ex­per­i­ments’ con­trols and off-tar­get edit­ing. Beam in­tends to re­spond to the hold let­ter, which the com­pa­ny says it re­ceived on Aug. 25, some­time in the fourth quar­ter this year.

Based on the lan­guage of the SEC fil­ing, it’s not en­tire­ly clear whether the FDA is re­quir­ing Beam to con­duct new pre­clin­i­cal stud­ies or sim­ply pro­vide ad­di­tion­al da­ta re­searchers al­ready have on hand. A com­pa­ny spokesper­son told End­points News that Beam will sup­ply reg­u­la­tors with “ad­di­tion­al da­ta and analy­sis with ex­ist­ing as­says.”

Specif­i­cal­ly in the fil­ing, Beam out­lined the FDA’s ask as the fol­low­ing:

  • (i) ad­di­tion­al con­trol da­ta from ge­nom­ic re­arrange­ment as­sess­ments;
  • (ii) fur­ther analy­ses of cer­tain off-tar­get edit­ing ex­per­i­ments;
  • (iii) ad­di­tion­al con­trol da­ta for a cy­tokine in­de­pen­dent growth as­say;
  • and (iv) an up­dat­ed in­ves­ti­ga­tor brochure that in­cludes in­for­ma­tion re­gard­ing any new non­clin­i­cal stud­ies

The pro­gram in ques­tion is an at­tempt at an al­lo­gene­ic, or off-the-shelf, CAR-T ther­a­py known as BEAM-201. The biotech is one of sev­er­al try­ing to de­vel­op these treat­ments de­rived from donor cells, rather than the tra­di­tion­al CAR-Ts that re-en­gi­neer a pa­tient’s own cells, to try to in­crease ac­ces­si­bil­i­ty and cut down on man­u­fac­tur­ing time.

Jef­feries an­a­lyst Michael Yee wrote to in­vestors Tues­day af­ter­noon that the fil­ing’s lan­guage sug­gests the FDA wants the com­pa­ny to run ad­di­tion­al stud­ies. Yee opines the stud­ies would help es­tab­lish “the lev­el of cel­lu­lar ex­pan­sion” and gen­er­ate more back­ground safe­ty da­ta be­fore sci­en­tists move the pro­gram in­to hu­man test­ing.

That way, “they can com­pare the edit­ed da­ta (once avail­able) to the con­trol and de­ter­mine if there are true safe­ty sig­nals (high­er in­ci­dence in the edit­ed sam­ples vs con­trol),” Yee writes.

Ad­di­tion­al­ly, Yee says the hold like­ly does not mean bad things are ahead for the rest of the com­pa­ny’s pipeline, writ­ing the is­sue here is prob­a­bly “be­nign” and “pre­ven­ta­tive.” When the news first dropped last month, Yee es­ti­mat­ed the hold would be re­solved with­in four to five months, a time­line he con­tin­ues to say is ac­cu­rate.

If Beam man­ages to clear the hold and get its IND ap­proved, BEAM-201 would be the com­pa­ny’s sec­ond base edit­ing pro­gram to en­ter the clin­ic. Pre­vi­ous­ly, the FDA waved through Beam’s sick­le cell dis­ease can­di­date for clin­i­cal test­ing last No­vem­ber, but as of last month the biotech had not yet be­gun re­cruit­ing pa­tients.

This ar­ti­cle has been up­dat­ed to in­clude com­ment from a Beam spokesper­son and out­side analy­sis from Jef­feries’ Michael Yee. 

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

I hope your weekend is off to a nice start, wherever you are reading this email. As for me, I’m trying to catch the tail of the Lunar New Year festivities.

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Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

Pfizer has laid off employees at its La Jolla, CA, and Groton, CT sites, according to multiple LinkedIn posts from former employees.

The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

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Filip Dubovsky, Novavax CMO

No­vavax gets ready to take an­oth­er shot at Covid vac­cine mar­ket with next sea­son plans

While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

Vaccines and Related Biological Products Advisory Committee (VRBPAC) members voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all future vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

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Steve Harr, Sana Biotechnology CEO

Four years in, Sana gets first FDA go-ahead to bring can­cer treat­ment in­to the clin­ic

Sana Biotechnology is finally headed to the clinic.

Thursday afternoon, the biotech announced the FDA had cleared its application to start a clinical trial for its allogeneic, or “off-the-shelf,” CAR-T cell therapy targeting the antigen CD19 for patients with B-cell lymphomas and leukemias. Sana said its therapy, dubbed SC291, was designed to evade the immune system, which could help cell therapy produce a more durable response in patients, a concern that has followed such off-the-shelf therapies that use donor cells as opposed to a patient’s own cells.

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CBER Director Peter Marks (Susan Walsh/AP Images)

FDA ad­vi­so­ry com­mit­tee votes unan­i­mous­ly in fa­vor of bi­va­lent Covid shots re­plac­ing pri­ma­ry se­ries

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all current vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

The vote marks an effort to clear up confusion around varying formulations and dosing schedules for current primary series and booster vaccines, as well as “get closer to the strains that are circulating,” according to committee member Paul Offit, professor of pediatrics at the Children’s Hospital of Philadelphia.

FDA re­ports ini­tial 'no sig­nal' for stroke risk with Pfiz­er boost­ers, launch­es con­comi­tant flu shot study

The FDA hasn’t detected any potential safety signals, including for stroke, in people aged 65 years and older who have received Pfizer’s bivalent Covid booster, one senior official told members of the agency’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Thursday.

The update comes as the FDA and CDC investigate a “preliminary signal” that may indicate an increased risk of ischemic stroke in older Americans who received Pfizer’s updated shot.

FDA cuts off use for As­traZeneca’s Covid-19 ther­a­py Evusheld

The FDA has stopped use of another drug as a result of the new coronavirus variants. On Thursday, the agency announced that AstraZeneca’s antibody combo Evusheld, which was an important prevention option for many immunocompromised people and others, is no longer authorized.

The FDA said it made its decision based on the fact that Evusheld works on fewer than 10% of circulating variants.

Evusheld was initially given emergency authorization at the end of 2021. However, as Omicron emerged, so did studies that showed Evusheld might not work against the dominant Omicron strain. In October, the FDA warned healthcare providers that Evusheld was useless against the Omicron subvariant BA.4.6. It followed that up with another announcement earlier this month that it did not think Evusheld would work against the latest Omicron subvariant XBB.1.5.

Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

Post-hoc analy­sis: EMA's CHMP re­jects Ipsen's po­ten­tial drug for rare ge­net­ic dis­ease

The European Medicines Agency’s Committee for Medicinal Products for Human Use on Friday rejected Ipsen Pharma’s potential treatment for a rare genetic disease known as fibrodysplasia ossificans progressiva (FOP), which causes extra bone to form outside the skeleton.

The EMA said on its website that it could not draw any firm conclusions on the benefits of the French biopharma’s Sohonos (palovarotene), which selectively targets the retinoic-acid receptor gamma (RARγ), “as the applicant’s conclusion was based on a post-hoc analysis which was neither scientifically nor clinically justified and pre-specified study objectives were not met.”

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